Low PD‐L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment

Abstract

Low PD-L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment Aims: The current criteria for surgical treatment after endoscopic resection of a pT1 colorectal carcinoma (CRC) are unsatisfactory because nodal involvement is rarely present. This study investigates the correlation between PD-L1 expression and nodal metastasis in pT1 CRCs to enable its use for tailoring surgical treatment after endoscopic removal. Methods and results: Histopathological features of 81 surgically resected pT1 CRC, 19 metastatic and 62 non-metastatic cases were assessed. PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and independently assessed by two pathologists using tumour proportion score (TPS), combined positive score (CPS) and immune cell score (ICS). The correlation between PD-L1 expression and nodal metastasis, the optimal cut-off values, interobserver agreement and impact upon patients' surgical management were determined. PD-L1 expression in terms of CPS and ICS independently correlated with lymph node metastasis (PD-L1 CPS : OR = -2.5, 95% CI = À4.11 to À0.97, P = 0.008 and PD-L1 ICS : OR = À1.85, 95% CI = À2.90 to À0.79, P = 0.004) and < 1.2 CPS and <1.3% ICS were identified as the optimal cut-off values to discriminate between metastatic and non-metastatic patients. In our cohort, the implementation of these cut-off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD-L1 CPS = 43.2; PD-L1 ICS = 51.9%). Ultimately, PD-L1 evaluation showed good interpathologist concordance in absolute terms [PD-L1 CPS interclass correlation coefficient (ICC) = 0.91; PD-L1 ICS ICC = 0.793] and using the identified cut-off values (PD-L1 CPS ICC = 0.848; PD-L1 ICS ICC = 0.756). Conclusions: Our study shows that PD-L1 expression is an effective predictor of nodal status and could improve patient selection for surgery after endoscopic removal of pT1 CRCs.

Lymph Node Molecular Analysis with OSNA Enables the Identification of pT1 CRC Patients at Risk of Recurrence: A Multicentre Study

“…In a recent meta-analysis, Zwager et al showed no significant association between LNM and the depth of submucosal infiltration [32]. A high histological grade is also considered to confer a higher risk for the presence of LNM, being consistently reported in the literature [5,7,8,16,29,30,32,[34][35][36][37][38]40,[45][46][47]51,52], while other studies have not found such a relationship [9,17,39,41,48]. In our study, we did not observe any association between a high histological grade and LNM.…”

“…Both TB and PDC have been proposed to be evaluated together in a "Combined Score", as they both may refer to the same biological phenomenon of epithelial-to-mesenchymal transition, but there is still some controversy among experts [42][43][44][45]. In addition, we also observed that the presence of LVI was associated with LNM when assessed with H&E. As is well known, the presence of LVI is a significant risk factor for LNM in pT1 CRC [5,[7][8][9][16][17][18]29,30,[35][36][37][38][39][40][41][46][47][48].…”